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51. Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke

Author

Barsic, Bruno, Dickerman, Stuart, Krajinovic, Vladimir, Pappas, Paul, Altclas, Javier, Carosi, Giampiero, Casabé, José H., Chu, Vivian H., Delahaye, Francois, Edathodu, Jameela, Fortes, Claudio Querido, Olaison, Lars, Pangercic, Ana, Patel, Mukesh, Rudez, Igor, Tamin, Syahidah Syed, Vincelj, Josip, Bayer, Arnold S., Wang, Andrew, Clara, Liliana, Sanchez, Marisa, Nacinovich, Francisco, Oses, Pablo Fernandez, Ronderos, Ricardo, Sucari, Adriana, Thierer, Jorge, Casabé, José, Cortes, Claudia, Kogan, Silvia, Spelman, Denis, Athan, Eugene, Harris, Owen, Kennedy, Karina, Tan, Ren, Gordon, David, Papanicolas, Lito, Eisen, Damon, Grigg, Leeanne, Street, Alan, Korman, Tony, Kotsanas, Despina, Dever, Robyn, Jones, Phillip, Konecny, Pam, Lawrence, Richard, Rees, David, Ryan, Suzanne, Feneley, Michael P., Harkness, John, Post, Jeffrey, Reinbott, Porl, Gattringer, Rainer, Wiesbauer, Franz, Andrade, Adriana Ribas, De Brito, Ana Cláudia Passos, Guimarães, Armenio Costa, Grinberg, Max, Mansur, Alfredo José, Siciliano, Rinaldo Focaccia, Strabelli, Tania Mara Varejao, Vieira, Marcelo Luiz Campos, De Medeiros Tranchesi, Regina Aparecida, Paiva, Marcelo Goulart, De Oliveira Ramos, Auristela, Ferraiuoli, Giovanna, Golebiovski, Wilma, Lamas, Cristiane, Santos, Marisa, Weksler, Clara, Karlowsky, James A., Keynan, Yoav, Morris, Andrew M., Rubinstein, Ethan, Jones, Sandra Braun, Garcia, Patricia, Cereceda, M., Fica, Alberto, Mella, Rodrigo Montagna, Bukovski, Suzana, Freiberger, Tomas, Pol, Jiri, Zaloudikova, Barbora, Ashour, Zainab, Kholy, Amani El, Mishaal, Marwa, Rizk, Hussien, Aissa, Neijla, Alauzet, Corentine, Alla, Francois, Campagnac, Catherine, Doco Lecompte, Thanh, Selton Suty, Christine, Casalta, Jean Paul, Fournier, Pierre Edouard, Habib, Gilbert, Raoult, Didier, Thuny, Franck, Delahaye, Armelle, Vandenesch, Francois, Donal, Erwan, Donnio, Pierre Yves, Michelet, Christian, Revest, Matthieu, Tattevin, Pierre, Violette, Jérémie, Chevalier, Florent, Jeu, Antoine, Rusinaru, Dan, Sorel, Claire, Tribouilloy, Christophe, Bernard, Yvette, Chirouze, Catherine, Hoen, Bruno, Leroy, Joel, Plesiat, Patrick, Naber, Germa Christoph, Neuerburg, Carl, Mazaheri, Bahram, Naber, Christoph, Athanasia, Sofia, Giannitsioti, Efthymia, Mylona, Elena, Paniara, Olga, Papanicolaou, Konstantinos, Pyros, John, Skoutelis, Athanasios, Sharma, Gautam, Francis, Johnson, Nair, Lathi, Thomas, D. M. Vinod, Venugopal, Krishnan, Hannan, Margaret, Hurley, John, Cahan, Amos, Gilon, Dan, Israel, Sarah, Korem, Maya, Strahilevitz, Jacob, Tripodi, Marie Françoise, Casillo, Roberta, Cuccurullo, Susanna, Dialetto, Giovanni, Durante Mangoni, Emanuele, Irene, Mattucci, Ragone, Enrico, Utili, Riccardo, Cecchi, Enrico, Rosa, Francesco De, Forno, Davide, Imazio, Massimo, Trinchero, Rita, Tebini, Alessandro, Grossi, PAOLO ANTONIO, Lattanzio, Mariangela, Toniolo, Antonio, Goglio, Antonio, Raglio, Annibale, Ravasio, Veronica, Rizzi, Marco, Suter, Fredy, Magri, Silvia, Signorini, Liana, Baban, Tania, Kanafani, Zeina, Kanj, Souha S., Sfeir, Jad, Yasmine, Mohamad, Abidin, Imran, Martínez, Eduardo Rivera, Nieto, Gabriel Israel Soto, Van Der Meer, Jan T. M., Chambers, Stephen, Murdoch, David R., Holland, David, Morris, Arthur, Raymond, Nigel, Read, Kerry, Dragulescu, Stefan, Ionac, Adina, Mornos, Cristian, Butkevich, O. M., Chipigina, Natalia, Kirill, Ozerecky, Vadim, Kulichenko, Vinogradova, Tatiana, Halim, Magid, Lum, Luh Nah, Tan, Ru San, Lejko Zupanc, Tatjana, Logar, Mateja, Mueller Premru, Manica, Commerford, Patrick, Commerford, Anita, Deetlefs, Eduan, Hansa, Cass, Ntsekhe, Mpiko, Almela, Manuel, Armero, Yolanda, Azqueta, Manuel, Castañeda, Ximena, Cervera, Carlos, Del Rio, Ana, Falces, Carlos, Garcia De La Maria, Cristina, Fita, Guillermina, Gatell, Jose M., Marco, Francesc, Mestres, Carlos A., Miró, José M., Moreno, Asuncion, Ninot, Salvador, Paré, Carlos, Pericas, Joan, Ramirez, Jose, Rovira, Irene, Sitges, Marta, Anguera, Ignasi, Font, Bernat, Guma, Joan Raimon, Bermejo, Javier, Bouza, Emilio, Fernández, Miguel Angel Garcia, Gonzalez Ramallo, Victor, Marín, Mercedes, Muñoz, Patricia, Pedromingo, Miguel, Roda, Jorge, Rodríguez Créixems, Marta, Solis, Jorge, Almirante, Benito, Fernandez Hidalgo, Nuria, Tornos, Pilar, De Alarcón, Arístides, Parra, Ricardo, Alestig, Eric, Johansson, Magnus, Snygg Martin, Ulrika, Pachirat, Orathai, Pachirat, Pimchitra, Pussadhamma, Burabha, Senthong, Vichai, Casey, Anna, Elliott, Tom, Lambert, Peter, Watkin, Richard, Eyton, Christina, Klein, John L., Bradley, Suzanne, Kauffman, Carol, Bedimo, Roger, Corey, G. Ralph, Crowley, Anna Lisa, Douglas, Pamela, Drew, Laura, Fowler, Vance G., Holland, Thomas, Lalani, Tahaniyat, Mudrick, Daniel, Samad, Zaniab, Sexton, Daniel, Stryjewski, Martin, Woods, Christopher W., Lerakis, Stamatios, Cantey, Robert, Steed, Lisa, Wray, Dannah, Dickerman, Stuart A., Bonilla, Hector, Di Persio, Joseph, Salstrom, Sara Jane, Baddley, John, Peterson, Gail, Stancoven, Amy, Afonso, Luis, Kulman, Theresa, Levine, Donald, Rybak, Michael, Cabell, Christopher H., Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Male, MESH: Endocarditis, Time Factors, Medizin, 030204 cardiovascular system & hematology, endocarditis, valve replacement, surgery, Cohort Studies, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Hospital Mortality, MESH: Inpatients, Stroke, MESH: Cohort Studies, MESH: Aged, MESH: Middle Aged, MESH: Cardiac Surgical Procedures, Endocarditis, Mortality rate, Hazard ratio, Middle Aged, stroke, 3. Good health, Cardiac surgery, Infectious Diseases, Infective endocarditis, Female, Cohort study, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Stroke, 03 medical and health sciences, medicine, Humans, MESH: Hospital Mortality, Cardiac Surgical Procedures, Aged, Inpatients, MESH: Humans, Proportional hazards model, business.industry, MESH: Time Factors, MESH: Adult, Odds ratio, medicine.disease, MESH: Male, Surgery, business, MESH: Female
Abstract

International audience; BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Published
2013

52. HACEK Infective Endocarditis: Characteristics and Outcomes from a Large, Multi-National Cohort

Author

Chambers, Stephen T, Murdoch, David, Morris, Arthur, Holland, David, Pappas, Paul, Almela, Manel, Fernández Hidalgo, Nuria, Almirante, Benito, Bouza, Emilio, Forno, Davide, Rio, Ana del, Hannan, Margaret M., Harkness, John, Kanafani, Zeina A., Lalani, Tahaniyat, Lang, Selwyn, Raymond, Nigel, Read, Kerry, Vinogradova, Tatiana, Woods, Christopher W., Wray, Dannah, Corey, G. Ralph, Chu, Vivian H., Clara, Liliana, Sanchez, Marisa, Nacinovich, Francisco, Oses, Pablo Fernandez, Ronderos, Ricardo, Sucari, Adriana, Thierer, Jorge, Casabé, José, Cortes, Claudia, Altclas, Javier, Silvia Kogan, Sanatorio, Spelman, Denis, Athan, Eugene, Harris, Owen, Kennedy, Karina, Tan, Ren, Gordon, David, Papanicolas, Lito, Eisen, Damon, Grigg, Leeanne, Street, Alan, Korman, Tony, Kotsanas, Despina, Dever, Robyn, Jones, Phillip, Konecny, Pam, Lawrence, Richard, Rees, David, Ryan, Suzanne, Feneley, Michael P., Post, Jeffrey, Reinbott, Porl, Gattringer, Rainer, Wiesbauer, Franz, Andrade, Adriana Ribas, de Brito, Ana Cláudia Passos, Guimarães, Armenio Costa, Grinberg, Max, Mansur, Alfredo José, Siciliano, Rinaldo Focaccia, Strabelli, Tania Mara Varejao, Vieira, Marcelo Luiz Campos, de Medeiros Tranchesi, Regina Aparecida, Paiva, Marcelo Goulart, Fortes, Claudio Querido, de Oliveira Ramos, Auristela, Ferraiuoli, Giovanna, Golebiovski, Wilma, Lamas, Cristiane, Santos, Marisa, Weksler, Clara, Karlowsky, James A., Keynan, Yoav, Morris, Andrew M., Rubinstein, Ethan, Jones, Sandra Braun, Garcia, Patricia, Cereceda, M., Fica, Alberto, Mella, Rodrigo Montagna, Barsic, Bruno, Bukovski, Suzana, Krajinovic, Vladimir, Pangercic, Ana, Rudez, Igor, Vincelj, Josip, Freiberger, Tomas, Pol, Jiri, Zaloudikova, Barbora, Ashour, Zainab, Kholy, Amani El, Mishaal, Marwa, Rizk, Hussien, Aissa, Neijla, Alauzet, Corentine, Alla, Francois, Campagnac, Catherine, Doco Lecompte, Thanh, Selton Suty, Christine, Casalta, Jean Paul, Fournier, Pierre Edouard, Habib, Gilbert, Raoult, Didier, Thuny, Franck, Delahaye, Francois, Delahaye, Armelle, Vandenesch, Francois, Donal, Erwan, Donnio, Pierre Yves, Michelet, Christian, Revest, Matthieu, Tattevin, Pierre, Violette, Jérémie, Chevalier, Florent, Jeu, Antoine, Rusinaru, Dan M. D., Sorel, Claire, Tribouilloy, Christophe, Bernard, Yvette, Chirouze, Catherine, Hoen, Bruno, Leroy, Joel, Plesiat, Patrick, Naber, Christoph, Neuerburg, Carl, Mazaheri, Bahram, Athanasia, Sofia, Giannitsioti, Efthymia, Mylona, Elena, Paniara, Olga, Papanicolaou, Konstantinos, Pyros, John, Skoutelis, Athanasios, Sharma, Gautam, Francis, Johnson, Nair, Lathi, Thomas, Vinod, Venugopal, Krishnan, Hannan, Margaret, Hurley, John, Gilon, Dan, Israel, Sarah, Korem, Maya, Strahilevitz, Jacob, Tripodi, Marie Françoise, Casillo, Roberta, Cuccurullo, Susanna, Dialetto, Giovanni, Durante Mangoni, Emanuele, Irene, Mattucci, Ragone, Enrico, Utili, Riccardo, Cecchi, Enrico, De Rosa, Francesco, Imazio, Massimo, Trinchero, Rita, Tebini, Alessandro, Grossi, PAOLO ANTONIO, Lattanzio, Mariangela, Toniolo, Antonio, Goglio, Antonio, Raglio, Annibale, Ravasio, Veronica, Rizzi, Marco, Suter, Fredy, Carosi, Giampiero, Magri, Silvia, Signorini, Liana, Baban, Tania, Kanafani, Zeina, Kanj, Souha S., Sfeir, Jad, Yasmine, Mohamad, Abidin, Imran, Tamin, Syahidah Syed, Martínez, Eduardo Rivera, Nieto, Gabriel Israel Soto, van der Meer, Jan T. M., Chambers, Stephen, Murdoch, David R., Dragulescu, Stefan, Ionac, Adina, Mornos, Cristian, Butkevich, O. M., Chipigina, Natalia, Kirill, Ozerecky, Vadim, Kulichenko, Edathodu, Jameela, Halim, Magid, Lum, Luh Nah, Tan, Ru San, Lejko Zupanc, Tatjana, Logar, Mateja, Mueller Premru, Manica, Commerford, Patrick, Commerford, Anita, Deetlefs, Eduan, Hansa, Cass, Ntsekhe, Mpiko, Almela, Manuel, Armero, Yolanda, Azqueta, Manuel, Castañeda, Ximena, Cervera, Carlos, Falces, Carlos, Garcia de la Maria, Cristina, Fita, Guillermina, Gatell, Jose M., Marco, Francesc, Mestres, Carlos A., Miró, José M., Moreno, Asuncion, Ninot, Salvador, Paré, Carlos, Pericas, Joan, Ramirez, Jose, Rovira, Irene, Sitges, Marta, Anguera, Ignasi, Font, Bernat, Guma, Joan Raimon, Bermejo, Javier, Fernández, Miguel Angel Garcia, Gonzalez Ramallo, Victor, Marín, Mercedes, Muñoz, Patricia, Pedromingo, Miguel, Roda, Jorge, Rodríguez Créixems, Marta, Solis, Jorge, Fernandez Hidalgo, Nuria, Tornos, Pilar, de Alarcón, Arístides, Parra, Ricardo, Alestig, Eric, Johansson, Magnus, Olaison, Lars, Snygg Martin, Ulrika, Pachirat, Orathai, Pachirat, Pimchitra, Pussadhamma, Burabha, Senthong, Vichai, Casey, Anna, Elliott, Tom, Lambert, Peter, Watkin, Richard, Eyton, Christina, Klein, John L., Bradley, Suzanne, Kauffman, Carol, Bedimo, Roger, Crowley, Anna Lisa, Douglas, Pamela, Drew, Laura, Fowler, Vance G., Holland, Thomas, Mudrick, Daniel, Samad, Zaniab, Sexton, Daniel, Stryjewski, Martin, Wang, Andrew, Lerakis, Stamatios, Cantey, Robert, Steed, Lisa, Dickerman, Stuart A., Bonilla, Hector, Dipersio, Joseph, Salstrom, Sara Jane, Baddley, John, Patel, Mukesh, Peterson, Gail, Stancoven, Amy, Afonso, Luis, Kulman, Theresa, Levine, Donald, Rybak, Michael, Cabell, Christopher H., Baloch, Khaula, Dixon, Christy C., Vance G., Fowler J. r., Harding, Tina, Jones Richmond, Marian, Park, Lawrence P., Redick, Thomas, Stafford, Judy, Anstrom, Kevin, Bayer, Arnold S., Karchmer, A. W., Sexton, Daniel J., Cabell, Christopher H, Chu, Vivian, Durack, David T., Eykyn, Susannah, Moreillon, Phillipe, Universitat de Barcelona, University of Otago [Dunedin, Nouvelle-Zélande], Auckland City Hospital, Microbiology Laboratory, Middlemore Hospital, Duke University Medical Center, Clinical and experimental neuroimmunology [IDIBAPS], Institut d'Investigacions Biomèdiques August Pi i Sunyer, Vall d'Hebron University Hospital [Barcelona], Hospital Universitario Gregorio Maranon, Hospital Universitario Gregorio Marañón, Cardiologie, Maria Vittoria Hospital [Turin], Mater Hospitals, University of New South Wales [Sydney] (UNSW), American University of Beirut [Beyrouth] (AUB), Uniformed Services University of the Health Sciences (USUHS), Wellington Hospital Private, Royal North Shore Hospital (RNSH), Russian State Medical University, Durham VA Medical Center, and University of South Carolina [Columbia]

Subjects
Aortic valve, Bacterial Diseases, Genetics and Molecular Biology (all), Valvular Disease, Medizin, Eikenella corrodens, Cardiobacterium, Infection control, Cardiovascular, American-heart-association, Biochemistry, Antimicrobial therapy, Cohort Studies, 0302 clinical medicine, Control d'infeccions, Diagnosis, Odds Ratio, Prevalence, 030212 general & internal medicine, Prospective cohort study, Haemophilus Influenzae, 0303 health sciences, Multidisciplinary, biology, Endocarditis, Medicine (all), Statistics, Congenital Heart Disease, Age Factors, Bacterial, 3. Good health, Management, Stroke, medicine.anatomical_structure, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Treatment Outcome, Infective endocarditis, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Medicine, Profile, Health-care professionals, Kingella, Cardiobacterium-hominis, Cohort study, Research Article, medicine.medical_specialty, Drugs and Devices, Science, Haemophilus, Referral bias, Statistics, Nonparametric, Medical Devices, 03 medical and health sciences, Internal medicine, Kingella Kingae Infection, medicine, Humans, Nonparametric, Aggregatibacter, Endocarditis, Bacterial, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Staphylococcus-aureus, Heart Failure, 030306 microbiology, business.industry, Acute Cardiovascular Problems, Bloodstream Infections, medicine.disease, biology.organism_classification, Surgery, Valve endocarditis, Cardiobacterium hominis, business
Abstract

International audience; The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p < 0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p < 0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p < 0.01) and younger age (OR 0.62; CI 0.49-0.90; p < 0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p < 0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Published
2013

54. Hypercalcemia in Necrobiotic Xanthogranuloma: First Reported Case and Insight Into Treatment.

Author

Sfeir, Jad G, Zogala, Richard J, and Popii, Violeta B

Abstract

ABSTRACT Necrobiotic xanthogranuloma (NXG) is a rare systemic and progressive granulomatous disease first described in 1980. Given no established first-line therapy, treatment focuses on the control of skin lesions and associated complications. Despite it being a granulomatous disease, NXG has not been associated with hypercalcemia. About 140 cases of NXG have been reported to date but, to our knowledge, this is the first case to be complicated by hypercalcemia. Our case confirms a granulomatous disease-mediated production of 1α-hydroxylase leading to increased synthesis of 1,25-dihydroxyvitamin D and subsequent hypercalcemia. Based on this pathophysiology, we elected to start systemic glucocorticoids, titrated to clinical and metabolic response. Steroid-sparing agents need to be considered to avoid long-term complications but continue controlling this granulomatous disease. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Published
2017
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56. In insulin-treated type 1 diabetes, canagliflozin increased diabetic ketoacidosis.

Author

Sfeir, Jad G. and Montori, Victor M.

Subjects
*COMBINATION drug therapy, *DIABETIC acidosis, *PEOPLE with diabetes, *FISHER exact test, *GLYCOSYLATED hemoglobin, *HYPOGLYCEMIC agents, *INSULIN, *TYPE 1 diabetes, *PROBABILITY theory, *STATISTICAL hypothesis testing, *BODY mass index, *RANDOMIZED controlled trials, *TREATMENT effectiveness, *DESCRIPTIVE statistics
Abstract

Question In adults with type 1 diabetes mellitus treated with insulin, does canaglifozin add-on treatment increase the risk for diabetic ketoacidosis (DKA)? Methods Design Randomized placebo-controlled trial. ClinicalTrials.gov NCT02139943. Allocation Unclear allocation concealment.* Blinding Blinded* {study sites and sponsor}†. Follow-up period 18 weeks. Setting Not reported. Patients 351 patients 25 to 65 years of age {mean age 42 y, 56% men}† who had type 1 diabetes for ≥1 year, hemoglobin (Hb) A1c level 7.0% to 9.0% (53 to 75 mmol/mol), body mass index 21 to 35 kg/m², and were receiving a stable insulin regimen (multiple daily injections or continuous subcutaneous infusion) for ≥8 weeks. Exclusion criteria included history of type 2 diabetes mellitus; DKA or severe hypoglycemic event in the past 6 months; myocardial infarction, unstable angina, coronary revascularization, or cerebrovascular accident in the past 12 weeks; history of New York Heart Association class III to IV cardiac disease; uncontrolled hypertension; estimated glomerular filtration rate >70 mL/min/1.73 m²; or treatment with an antihyperglycemic other than insulin in the past 12 weeks. Intervention Canagliflozin, 100 mg (n=117), canagliflozin, 300 mg (n=117), or placebo (n=117) once/d before the first meal. Outcomes Safety outcomes included ketone-related adverse events (i.e., acidosis, blood ketone body increased, blood ketone body present, DKA, diabetic ketoacidotic hyperglycemic coma, ketoacidosis, ketonemia, ketonuria, ketosis, metabolic acidosis, or urine ketone body present) and serious DKA. Patient follow-up 93%† (modified intention-to-treat analysis). Main results Risks for any ketone-related adverse events and for serious DKA events requiring hospitalization were increased with canagliflozin compared with placebo (Table). Conclusion In patients with insulin-treated type 1 diabetes mellitus, canagliflozin increased diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

Published
2016
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57. A retrospective cohort of tumor-induced osteomalacia and case series of malignant disease.

Author

Hoong CWS, Sfeir J, Algeciras-Schimnich A, and Clarke BL

Abstract

Objective: We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with tumor-induced osteomalacia (TIO), with a focus on patients with non-localizing and malignant TIO., Methods: This is a retrospective cohort of TIO patients in an academic medical center, diagnosed between January 1998 to May 2023. We described their demographics, biochemistries, tumor features, localization, treatment and complications., Results: Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. 20 (40%) had persistent disease due to wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus or baseline fibroblast growth factor-23 (FGF23) levels between localizing versus non-localizing groups, and malignant versus non-malignant groups. Lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. 60% of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R=0.566, p<0.001) but was not associated with malignancy risk (p=0.479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (p=0.025), and recurrence after initial cure (p=0.013) were factors significantly associated with malignancy. The non-localizing group had lower survival than localizing group (p=0.0097)., Conclusions: TIO is a condition with significant morbidity. Very high FGF23 level and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in non-localizing TIO should be further explored., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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58. In vitro and in vivo effects of zoledronate on senescence and senescence-associated secretory phenotype markers.

Author

Samakkarnthai P, Saul D, Zhang L, Aversa Z, Doolittle ML, Sfeir JG, Kaur J, Atkinson EJ, Edwards JR, Russell RGG, Pignolo RJ, Kirkland JL, Tchkonia T, Niedernhofer LJ, Monroe DG, LeBrasseur NK, Farr JN, Robbins PD, and Khosla S

Abstract

In addition to reducing fracture risk, zoledronate has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronate could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronate killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronate or vehicle for 8 weeks, zoledronate significantly reduced circulating SASP factors, including CCL7, IL-1β, TNFRSF1A, and TGFβ1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronate demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronate, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronate significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronate has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo . These data point to the need for additional studies testing zoledronate and/or other bisphosphonate derivatives for senotherapeutic efficacy.

Published
2023
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59. Vertebral compression fractures associated with yoga: a case series.

Author

Sfeir JG, Drake MT, Sonawane VJ, and Sinaki M

Subjects
Aged, Cohort Studies, Female, Humans, Middle Aged, Risk Factors, Fractures, Compression diagnosis, Fractures, Compression etiology, Spinal Fractures diagnosis, Spinal Fractures etiology, Yoga
Abstract

Background: The importance of exercise in skeletal health is increasingly recognized by both patients and providers. However, the safety of prescribed or recreational exercise in at-risk populations remains under-reported and under-publicized. Yoga has gained widespread popularity due to its physical and psychological benefits. When practiced in a population at increased fracture risk, however, some yoga poses may increase fracture risk, particularly at the spine, rather than increasing BMD as noted in recent popular press reports., Case Report: Nine subjects (8 women) with a median age of 66 years (range 53-87), developed vertebral compression fracture (VCF) one month to six years after initiating yoga-associated spinal flexion exercises (SFE). VCF presented with back pain and occurred in the thoracicspine (N.=6), lumbar-spine (N.=4) and cervical-spine (N.=1). Four patients had osteoporosis by BMD criteria prior to VCF and 2 had osteopenia (median T-score -2.35; range -3.3 to +2.0). Interestingly, all patients had their lowest T-scores at the spine. Three patients had a history of fragility fracture prior to the index VCF. While one patient had primary hyperparathyroidism and another was treated with high dose prednisone, no other risk factors for bone loss including medications or secondary osteoporosis causes were identified in the other patients., Clinical Rehabilitation Impact: This study identified patients in whom increased torsional and compressive mechanical loading pressures occurring during yoga SFE resulted in de novo VCF. Despite the need for selectivity in yoga poses in populations at increased fracture risk, both scientific and media reports continue to advertise yoga as a bone protective activity. Accordingly, yoga is misconceived as a 'onesize-fits-all' prescription. Instead, the appropriate selection of patients likely to benefit from yoga must be a cornerstone of fracture prevention.

Published
2018
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